Genetic Variant RBM5:p.Ala330Ala (chr3-50107518-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005778.4(RBM5):c.990T>C(p.Ala330Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,607,944 control chromosomes in the GnomAD database, including 306,052 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 33083 hom., cov: 30)

Exomes 𝑓: 0.61 ( 272969 hom. )

Consequence

RBM5
NM_005778.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

Publications

43 publications found

Variant links:

Genes affected

RBM5 (HGNC:9902): (RNA binding motif protein 5) This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer. [provided by RefSeq, Oct 2011]

RBM5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP7

Synonymous conserved (PhyloP=0.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM5	NM_005778.4 link	c.990T>C	p.Ala330Ala	synonymous_variant	Exon 12 of 25	ENST00000347869.8	NP_005769.1	P52756-1A0A024R2U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM5	ENST00000347869.8 link	c.990T>C	p.Ala330Ala	synonymous_variant	Exon 12 of 25	1	NM_005778.4	ENSP00000343054.3		P52756-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99201

AN:

151794

Hom.:

33037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.741

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.639

GnomAD2 exomes

AF:

0.675

AC:

169641

AN:

251448

AF XY:

0.673

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.621

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.605

AC:

881612

AN:

1456032

Hom.:

272969

Cov.:

AF XY:

0.610

AC XY:

442365

AN XY:

724758

show subpopulations

African (AFR)

AF:

0.733

AC:

24440

AN:

33334

American (AMR)

AF:

0.752

AC:

33609

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

19121

AN:

26088

East Asian (EAS)

AF:

0.871

AC:

34522

AN:

39654

South Asian (SAS)

AF:

0.822

AC:

70829

AN:

86142

European-Finnish (FIN)

AF:

0.617

AC:

32955

AN:

53404

Middle Eastern (MID)

AF:

0.650

AC:

3743

AN:

5756

European-Non Finnish (NFE)

AF:

0.565

AC:

624858

AN:

1106732

Other (OTH)

AF:

0.623

AC:

37535

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15976

31952

47929

63905

79881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.654

AC:

99300

AN:

151912

Hom.:

33083

Cov.:

AF XY:

0.662

AC XY:

49132

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.729

AC:

30188

AN:

41416

American (AMR)

AF:

0.679

AC:

10367

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.741

AC:

2570

AN:

3470

East Asian (EAS)

AF:

0.886

AC:

4577

AN:

5166

South Asian (SAS)

AF:

0.828

AC:

3982

AN:

4808

European-Finnish (FIN)

AF:

0.619

AC:

6516

AN:

10520

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.575

AC:

39062

AN:

67954

Other (OTH)

AF:

0.636

AC:

1342

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1706

3411

5117

6822

8528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.605

Hom.:

61653

Bravo

AF:

0.655

Asia WGS

AF:

0.798

AC:

2776

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.20

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr3-50107518-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over